Solid tumor growth proceeds in conncert with tumor vascularization, which requires as essential components, endothelial cells of the host capillary system and a tumor-produced mitogenic substance, the angiogenesis factor (AF). We have developed an in vitro model system, in which cultured endothelial cells from fetal bovine aorta show a stimulation in growth in response to tumor-derived substances present in the medium (Fenselau and Mello, Cancer Res. 36, 3269 (1976)). We propose to examine various aspects of the phenomenon of tumor vascularization using this in vitro model system. These features include studies on the purification and characterization of the tumor AF from the Walker 256 carcinoma, on the relationship of this agent(s) to AF from other tumors and to other known cellular growth factors, on the production and release of the tumor AF, on actual or potential antiangiogenic agents, and on the mechanisms of action by which these growth factors (both stimulators and inhibitors) affect endothelial cell growth. In sum the thrust of these efforts is to better understand the entire process of tumor vascularization, and ultimately to be able to control this process and consequently tumor growth as well as spread.